"These data almost 10 years later," Healy said, "showing a fivefold increased risk in heart defects and a tenfold increased risk in birth defects in general has not been published."
Second Expert Opinion
During her testimony, Kramer also went over Glaxo's meta-analysis and explained what it showed. "GSK determined that the odds ratio for cardiac malformation as a broad class was 1.48," she told the jury. "That is a 48-percent increased risk where they have combined data from all of the studies that they could find to date."
"They also found an odds ratio of 1.67 for septal defects," she said. "That is a 67-percent increased risk of septal defects associated with first trimester Paroxetine exposure for all the studies, for the three studies where there was actually data on septal defects."
"And then for their summary odds ratio for right ventricular outflow tract obstruction defects," she added, "the two case control studies which actually looked at those types of defects they found a summary odds ratio of 2.85."
Most of the studies in the meta-analysis did not break down the cardiac defects into subcategories, Kramer said. "Either because they simply didn't have enough individuals in their studies or they set up their study rules which preclude them from doing so."
It would be inappropriate to conclude that if a specific cardiac defect was not found in these studies that Paxil did not cause it, she said. "It would be very much inappropriate and erroneous to assume that because that subcategory is not mentioned ... that there is no increased risk associated with it."
Kramer also testified about the Wurst study, published only 12 or 13 days before she testified. The "GlaxoSmithKline meta-analysis that we just discussed was not published," she told the jury. The "Wurst study is the published version ... but updated with one additional study."
She was asked whether there was anything new or different in the Wurst study. "Well, the only thing that is different in ... the published version versus unpublished version," she said, "is that they did not publish any subgroupings of cardiac abnormalities, birth defects in the published version."
They only "analyzed and published the summary odds ratio for all cardiac birth defects combined," she noted.
"And that summary odds ratio was very similar to the first one," she said. "It's 1.46. That is a 46-percent increased risk for all cardiac defects combined."
During cross-examination, Glaxo attorney, Todd Davis, told Kramer, "despite every single one of those studies looking at that those different patient populations over different time periods, there is not a single case in any of the studies that you talked about ... that identifies a patient who was exposed to Paroxetine or Paxil who had an IAA ..."
He noted that Lyam "was diagnosed with an interrupted aortic arch Type A," and asked Kramer: "Can you -- can you point to the jury in your report where you mention anything about interrupted aortic arch of any kind?"
"I probably didn't because there is no specific study that analyzed that specific defect as a stand alone category," she replied.
Kramer pointed out that "the epidemiological studies that have been conducted never individually analyzed the rates of the risk of interrupted aortic arch Type A associated with first trimester Paxil exposure."
Because it is so very rare, she said, it would be impossible to do given the required sample size of "something over a million" subjects in order to conduct such a study.
